Monoclonal antibodies which bind preferentially to human lung tumors are potentially important diagnostic and therapeutic reagents. A panel of these antibodies which have already been developed will be applied to three related projects. In the first project the monoclonal antibodies are covalently attached to the surface of lipid vechiles which contain cytotoxic drugs. The ability of the antibody-coupled liposomes to kill tumor cells in vitro and in vivo (tumors carried in nude mice) will be tested and compared to the tumorocidal activity of liposomes that do not contain antibody. We recognize that selective destruction of tumor cells via the immunospecific targeting of drug-containing loposomes will require a major effort in the development and improvement of current technogies. Until recently this approach to liposome targeting has been severely limited by the lack of an efficient method for the attachment of antibodies to the surface of liposomes. Utilizing a unique heterobifunctional cross-linking reagent N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) we and others have now shown that it is possible to couple monoclonal antibodies to erythrocyte and lymphocyte cell membranes (Jou and Bankert 1981) or to the surface of lioposomes (Martin et al 1981) without any noticible loss in the antibodies' antigen-binding activity. In the second project the monoclonal antibodies will be used to isolate and to characterize membrane macromolecules of selected lung tumors. Individual as well as combinations of monoclonal antibodies will be used in the affinity-chromatographic purification of putative tumor-associated antigens. Antigens identified in this project may be used in a lung cancer immunotherapy program which is currently in progress at our Institute. In the third project, monoclonal antibodies and tumor-associated antigens will be used in an attempt to develop immunodiagnostic assays which detect antigens/antibodies associated with the presence and growth of a patient's lung tumor. Using antibodies/antigens attached via SPDP to erythrocytes in a modified immune hemolytic assay we have detected as little as 10 picograms of specific test antigens/antibodies. By screening a large panel of monoclonal antibodies we seek to identify one or more antibodies which when coupled to erythrocytes would identify and antigen in the sera of bronchial washings of patients which correlates with the active proliferation of a patient's lung tumor.